Neovascularization in mature adult tissues is a tightly regulated process that can occur in a number physiological and pathophysiological conditions. In particular, myocardial collateral vessels in coronary circulation can develop in response to progressive coronary artery occlusion. These coronary collaterals are natural bypass vessels that can develop in the ischemic areas of the heart to provide an alternate route for nutrient blood supply. Typical myocardial collaterals are small thin-walled vessels, ranging from about forty to about two hundred micrometers in diameter, and their presence is an indication of advanced coronary disease. Although coronary collaterals are not detected in all patients with advanced coronary disease, their presence is associated with smaller infarcts and a more benign clinical course. Sufficient collateralization can prevent the damage of heart attack. Beyond its significance in a cardiac setting, neovascularization is also a hallmark of cancer growth. For both of these reasons, identification of collateral circulation is clinically important. Despite its value, identification of collateralized tissue has to date been quite limited due to the insensitivity of presently available detection techniques. These techniques include contrast angiography that can identify vessels greater than about one hundred eighty micrometers in size, and various nuclear perfusion cardiac imaging techniques that identify areas with preserved blood supply.
Several conventional technologies seek to therapeutically stimulate growth of collateral vessels. These include a number of heparin-binding growth factors that augment the growth and formation of coronary collateral circulation in the setting of myocardial ischemia. Other physical, mechanical or biochemical treatments have also been proposed as potential promoters of neovascularization, including techniques such as creating burns into the myocardium. However, these technologies are still too immature for implementation in successful treatment protocols. The ability to image the affected tissue is extremely limited; presently, there are no reliable noninvasive techniques capable of identifying and tracking the development of collateral vessels. Neovascularization is also important in cancer control, where the goal is to impede new vessel development which supports tumours.
The present invention seeks to address this problem, and a more general tissue imaging problem, by resolving several limitations of magnetic resonance imaging (MRI) to form images of clinical utility.
There remains a need for an effective method and device to image small sparse targets such as neovascularization and collateral vessels in vivo.
There is also a need for MRI protocols which can enhance contrast or more effectively resolve features relevant to a range of diagnostic criteria, particularly criteria based on perfusion, neovascularization, or small vessel activity in the tissue under consideration.